eLife, 2017-07, Vol.6
2017
Details
- Autor(en) / Beteiligte
- Titel
- Synthetic lethality between the cohesin subunits STAG1 and STAG2 in diverse cancer contexts
- Ist Teil von
- eLife, 2017-07, Vol.6
- Ort / Verlag
- England: eLife Science Publications, Ltd
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Recent genome analyses have identified recurrent mutations in the cohesin complex in a wide range of human cancers. Here we demonstrate that the most frequently mutated subunit of the cohesin complex, , displays a strong synthetic lethal interaction with its paralog . Mechanistically, STAG1 loss abrogates sister chromatid cohesion in mutated but not in wild-type cells leading to mitotic catastrophe, defective cell division and apoptosis. STAG1 inactivation inhibits the proliferation of STAG2 mutated but not wild-type bladder cancer and Ewing sarcoma cell lines. Restoration of STAG2 expression in a mutated bladder cancer model alleviates the dependency on STAG1. Thus, STAG1 and STAG2 support sister chromatid cohesion to redundantly ensure cell survival. STAG1 represents a vulnerability of cancer cells carrying mutations in the major emerging tumor suppressor across different cancer contexts. Exploiting synthetic lethal interactions to target recurrent cohesin mutations in cancer, e.g. by inhibiting STAG1, holds the promise for the development of selective therapeutics.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2050-084XeISSN: 2050-084XDOI: 10.7554/elife.26980Titel-ID: cdi_doaj_primary_oai_doaj_org_article_2300278a425a41e0beb781865da52db9
- Format
- –
- Schlagworte
- Antigens, Nuclear - genetics, Antigens, Nuclear - metabolism, Apoptosis, Cancer, Cancer Biology, Carcinogenesis, Cell Biology, Cell Cycle Proteins, Cell Division, Cell Line, Tumor, Cell Survival, Cellular proteins, Chromosomes, Cloning, Cohesin, Drinking water, Drug development, Ewing's sarcoma, Gene expression, Gene mutation, Genetic aspects, Genetic interaction, Genomes, Health aspects, Human, Humans, Innovations, Lethality, Leukemia, Medical research, Mitosis, Molecular targeted therapy, Mutation, Nuclear Proteins - genetics, Nuclear Proteins - metabolism, Proteins, Short Report, Synthetic Lethal Mutations, Synthetic lethality, Tumor cell lines, Tumor suppressor genes, Tumorigenesis, Tumors, Urinary bladder